Carnitine (vitamin Bt; 3-hydroxy-4-trimethylammonio-butanoate) is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine. In living cells, it is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids for the generation of metabolic energy. It is used as a nutritional supplement. Carnitine exists in two stereoisomers. The biologically active form is L-carnitine, whilst its enantiomer, D-carnitine, is biologically inactive. When producing L-carnitine in an industrial process, it is desirable to produce the biologically active L-form in high purity.
Various methods were described for the industrial production of L-carnitine. Microbiological processes are known, in which L-carnitine is produced directly by bacteria. In other processes, a racemate is produced by organic synthesis and separated subsequently into enantiomers.
Methods have been described for producing L-carnitine by chiral synthesis in the presence of asymmetric catalysts. In this respect, Santaniello et al. (1984) disclose the direct production of chiral L-carnitine from various precursors. In a specific approach, a ketoester corresponding to carnitine is reduced in the presence of an asymmetric catalyst, followed by the reaction of the product with trimethylamine in order to obtain L-carnitine. The authors also suggest producing L-carnitine from a β-lactam cyclic precursor.
Attempts have been made to synthesize. L-carnitine from β-lactone intermediates. In principle, β-lactones are available by [2+2] cycloadditions of ketenes and aldehydes. Chiral catalysts for obtaining chiral β-lactones were originally described by Wynberg et al. (1982). The authors found that a cycloaddition reaction could be carried out in the presence of a chiral quinidine catalyst. However, the availability of β-lactones suitable for carnitine synthesis is severely limited, because the reactions usually require activated ketones or aldehydes.
Based on the findings of Wynberg et al., Song et al. (1995) developed a full synthesis of L-carnitine starting from chloral (trichloroethanal) and ketene. The overall reaction is shown in scheme 1 below.

After the ring opening reaction, two chlorine atoms have to be eliminated from the carnitine precursor. Several steps are necessary to convert the trichloral ester into the corresponding monochlorinated equivalent before final conversion into carnitine. This renders the overall process time consuming and complicated. Further, the method requires chloral and tin organic reactants, which are toxic. Since carnitine is usually required for food or feed applications, it is desirable to avoid such toxic substances. Further, n—Bu3SnH has to be produced in situ, which is relatively complicated. In view of these drawbacks, the industrial applicability of this pathway is severely limited.
Since chiral L-carnitine is an important industrial product, it would be desirable to provide alternative efficient processes for its production. Specifically, it would be desirable to provide processes which allow the production of L-carnitine in a relatively simple manner and at a high yield.